Lymphomas affecting the submandibular glands / Linfomas que afectan las glándulas submandibulares

Background: Lymphomas affecting the submandibular glands are very uncommon and few reports are currentlyavailable in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic fea-tures of an original series of lymphomas affecting the submandibular glands.Material and Methods: The pathology files of two institutions were searched for lymphoma cases affecting thesubmandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by apathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation,treatment, follow-up and status at last appointment were retrieved from the patients’ medical charts.Results: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with amean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma representedthe most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patientsdied, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma.Conclusions: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other sub-types may also be rarely diagnosed in this salivary gland.(AU)

Role of miRNAs in Sigmoid Colon Cancer: A Search for Potential Biomarkers.

The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values < 0.05 and |Log2(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.

Adenocarcinomas do estômago relacionados com o vírus de Epstein-Barr: estudo dos aspectos clínico-patológicos e a relação com o infiltrado linfocitário com ênfase na expressão de PD-L1 / Gastric adenocarcinoma associated with Epstein-Barr virus: a clinical-pathological study and the relationship to lymphocytic infiltrates with focus on PD-L1 expression

O adenocarcinoma gástrico associado ao vírus Epstein-Barr (EBV) corresponde a cerca de 10% dos carcinomas gástricos, ocorre mais frequentemente em pacientes mais jovens e acomete preferencialmente a porção proximal do estômago. São tumores que com maior frequência exibem um crescimento sólido, associado a um infiltrado linfocitário exuberante. A imunoterapia tem trazido uma nova perspectiva para o tratamento de vários tumores e consequentemente a avaliação do PD-L1 tem sido amplamente estudada, incluindo tumores gástricos. Foram avaliados 269 casos de adenocarcinomas gástrico operados na Liga contra o câncer do estado do Rio Grande do Norte com a finalidade de avaliar os dados clínico-patológicos, a frequência de casos associados a EBV, a expressão de PD-L1 e p16 e o infiltrado de linfócitos CD8 e CD4 intra e peritumorais. Foram identificados 17 casos (6,32%) de adenocarcinomas associados à EBV (AdG-EBV). Estes ocorreram mais frequentemente em pacientes acima de 50 anos (60%), com estádio T3/T4 em 94,12% e com acometimento linfonodal em 84,03%. O infiltrado linfocitário CD8 e CD4 positivos foi observado em todos os casos, expressão de PD-L1 em 82,35%% e de p16 em 35,29% dos tumores. Nos adenocarcinomas não associados à EBV (AdG-não-EBV) houve predomínio em pacientes acima de 50 anos, com estádio T3/T4 em 79,6%, com acometimento linfonodal em 65,48%, infiltrado linfocitário CD8 e CD4 positivos em 66,5% e 73,02 respectivamente e expressão de p16 em 67,86% dos tumores. Foi demonstrado uma menor frequência de AdG-EBV no presente estudo quando comparado com a literatura. A grande maioria acomenteu pacientes acima de 50 anos, estava em estádios avançados e com linfonodos acomentidos semelhantes aos tumores não associados à EBV. Porém, mais frequentemente expressaram PD-L1 e com infiltrado de linfócitos CD8 e CD4 positivos. O p16 foi expresso em menor frequência, não sendo possível ser usado como um biomarcador da infecção pelo EBV

Gastric adenocarcinoma associated with the Epstein-Barr virus (EBV) corresponds to about 10% of gastric carcinomas, occurs more frequently in younger patients and affects the proximal portion of the stomach preferentially. They are tumours that more frequently exhibit a solid growth, associated with an exuberant lymphocytic infiltrate. Immunotherapy has been placed into a new perspective for the treatment of several tumours and consequently the assessment of PD-L1 has been extensively studied, including in gastric tumours. 269 cases of gastric adenocarcinomas were analyzed in the Liga Contra o Cancer in the state of Rio Grande do Norte in order to evaluate the clinical-pathological data, frequency of cases associated with EBV, PD-L1 and p16 status and infiltrate of CD8 and CD4 lymphocytes intra and peritumoral. It was identified 17 cases (6.32%) of EBV-associated adenocarcinomas (AdG-EBV). These occurred more frequently in patients over 50 years (60%), with T3 / T4 stage in 94.12% and with lymph node involvement in 84.03%. CD8 and CD4 positive lymphocytic infiltrates were observed in all cases, PD-L1 expression in 82.35% and p16 in 35.29% of tumours. Adenocarcinomas not associated with EBV (AdG-non-EBV) were predominant in patients over 50 years of age, with T3 / T4 stage in 79.6%, with lymph node involvement in 65.48%, CD8 and CD4 lymphocytic infiltrate in 66, 5% and 73.02 respectively and p16 expression in 67.86% of the tumours. A lower frequency of AdG-EBV was demonstrated in the present study when compared with the literature. The vast majority of the cases occurred in patients over 50 years of age, in advanced stages and with lymph nodes metastasis similar to tumours not associated with EBV. However, they more frequently expressed PD-L1 and with CD8 and CD4 positive lymphocyte infiltrates. P16 was expressed less frequently and could not be used as a biomarker of EBV infection

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features.

AIM: To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population. METHODS: One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients' clinical charts, intra-operative documentation, and pathology scoring. RESULTS: Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk. CONCLUSION: The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

Identification of a new BRCA2 large genomic deletion associated with high risk male breast cancer.

BACKGROUND: Male breast cancer (MBC) is an uncommon disease that has been the focus of limited research. It is estimated that approximately 10% of men with breast cancer have a genetic predisposition, with BRCA2 being the most prevalent genetic mutation. Here we describe the case of MBC in a 64-year-old man who presented on physical examination a nodule in his left breast and declared to have an extensive family history of cancer. METHODS AND RESULTS: The patient was firstly diagnosed with an invasive ductal carcinoma (IDC) with histological grade III, nuclear grade 3, pT4N2Mx and positive for hormonal receptors and HER2. Exome sequencing was performed by massive parallel sequencing which had detected a novel BRCA2 germline mutation that is a large genomic deletion of 3,492 nucleotides including BRCA2 exon 14, and this deletion is out of frame and is predicted to lead to a stop codon in exon 15 at codon 2,496. CONCLUSION: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer. This is the first report of the mutation del3492 in BRCA2 exon 14, which leads to a truncated protein and therefore is clinically relevant. Mutation segregation analysis should be further done in the Brazilian population. Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

Aspectos histoquímicos da membrana basal associados a variáveis clínicas em carcinoma epidermóide oral / Histochemical aspects of the basal membrane associated with clinical variables in oral squamous cell carcinoma

Objetivo: Avaliar o comportamento da membrana basal em lesões do carcinoma epidermóide oral, relacionando esse comportamento com a classificação clínica TNM, localização anatômica e sobrevida dos pacientes. Método: O estudo foi baseado em uma revisão retrospectiva incluindo a observação histológica de 20 casos de carcinoma epidermóide oral dos arquivos do Laboratório de Patologia do Hospital Estadual Dr. Luis Antônio em Natal, RN, Brasil. Com a análise dos prontuários médicos, foram obtidos os dados referentes à classificação clínica TNM e localização anatômica. A gradação histológica de malignidade foi realizada na área invasiva do tumor por dois patologistas em secções histológicas de 3 micrometros de espessura coradas pela hematoxilina e eosina (HE), para obtenção dos escores histológicos de malignidade, e pelo ácido periódico de Schiff (PAS) para o estudo da membrana basal. Resultados: O principal padrão de marcação da membrana basal foi contínuo, variando entre fraco, moderado e intenso, em lesões com baixo escore de malignidade e principalmente localizadas no lábio com a maioria dos pacientes livres da doença. Em lesões reincidentes principalmente em língua, com alto escore de malignidade, o padrão mais evidente de marcação da membrana basal foi descontínuo ou ausente. Conclusão: Lesões de língua com membrana basal descontínua ou ausente em pacientes com estadiamento clínico TNM III ou IV estão relacionadas com um prognóstico desfavorável, ao contrário, das lesões em lábio com a membrana basal contínua e estadiamento clínico TNM I ou II.

Objective: To evaluate the behavior of the basal membrane in oral squamous cell carcinoma lesions, relating this behavior to the TNM clinical classification, anatomic location and patient survival rate. Method: The study was based on a retrospective review, including the histological examination of 20 oral squamous cell carcinoma cases from the fi les of the Dr. Luis Antonio State Hospital's Pathology Laboratory in the city of Natal, RN, Brazil. Data referring to TNM clinical classification and anatomic location were obtained from the analysis of medical records. The histological grading of malignancy was made by the analysis of 3-micrometrics - thick histological sections stained with hematoxylin and eosin by two pathologists in order to obtain the histological malignancy scores, and by the periodic acid-Schiff (PAS) for the analysis of the basal membrane. Results: The main labeling pattern of the basal membrane was continuous, varying among weak, moderate and severe in lesions with low malignancy scores and were predominantly located in the lower lip in most healthy patients. For the recurrent lesions, mainly located on the tongue, with high malignancy scores, the most evident basal membrane labeling pattern was discontinuous or absent. Conclusion: Tongue lesions with discontinuous or absent basal membrane in patients in the III or IV TNM clinical stages are related to a poor prognosis, unlike lip lesions with continuous basal membrane and classified as I or II TNM clinical stages.

Tumor estromal gástrico apresentando-se com quadro de hemoperitôneo / Gastric stromal tumor presented as hemorrhagic ascites

O tumor estromal gástrico (GIST) é uma neoplasia rara que acomete, principalmente, pacientes acima de 50 anos de idade, sem predileção pelo sexo. Entre suas manifestações clínicas, destacam-se anemia, hemorragia gastrointestinal, dor abdominal e massa palpável. O caso clínico relatado é de um paciente masculino de 38 anos, apresentando queixas de dor abdominal difusa com predomínio em região epigástrica associada a anemia, perda de peso e constipação intestinal, com dois meses de evolução. Ao exame, encontrava-se com estado geral bom, descorado (+++/4+), abdome globoso, doloroso à palpação e sinal de piparote positivo. A endoscopia digestiva alta evidenciou lesão polipóide séssil com ulceração central em grande curvatura, sendo biopsiada e negativa para malignidade. A tomografia computadorizada (TC) de abdome mostrou presença de volumosa lesão ovalar, medindo cerca de 20 x 13cm em seus maiores eixos, localizada ao nível do meso e hipogástrio, associada à presença de líquido livre na cavidade abdominal. Submetido à laparotomia exploradora, foi evidenciada ascite hemorrágica importante e presença de grande tumoração cística aderida à grande curvatura do estômago. Realizou-se gastrectomia subtotal com reconstrução em Y de Roux. O laudo histopatológico revelou tumor estromal gástrico maligno. Encontra-se assintomático e livre de doença após 24 meses.

Repercussões histopatológicas da colostomia no coto colônico distal desfuncionalizado: estudo experimental em ratos / Histopathological consequences of colostomy in the defunctional intestinal segment: an experimental study in rats

O objetivo deste trabalho foi evidenciar as repercussões histopatológicas da colostomia no segmento desfuncionalizado e, dessa forma, criar um modelo experimental da colite de derivação fecal (CD). Foram utilizados 65 ratos, adultos, da raça Wistar, com peso variando de 220 a 300g. Os animais foram divididos em 13 grupos, contendo cinco ratos. Do grupo 1 ao grupo 12, os animais foram submetidos a laparotomia mediana, sendo realizada uma colostomia terminal tipo boca única, e observados, por períodos variados de tempo, com o máximo de cem dias. Os animais, após serem mortos, foram necropsiados e retirado o segmento colônico desfuncionalizado para a avaliação histopatológica. Essa avaliação consistia de uma análise quantitativa, através da medida da espessura da mucosa colônica, e de uma análise qualitativa, mediante avaliação subjetiva: da presença de infiltrado inflamatório agudo ou crônico na lâmina própria; das alterações na arquitetura das criptas colônicas; da presença de hiperplasia folicular linfóide e de linfócitos na luz dos vasos da submucosa; e da presença de eosinófilos na luz intestinal. No grupo 12, após o 100 dia de pós-operatório (DPO), foi realizada a reconstrução do trânsito intestinal, e, após trinta dias, o cólon descendente foi retirado para a análise histopatológica. O método de Tukey e o teste "t" de Student foram utilizados como parte da análise dos resultados. Verificou-se uma redução estatisticamente significante da espessura da mucosa colônica a partir do 40 DPO. Concluiu-se que a colostomia desfuncionalizante realizada em ratos reproduziu alterações histopatológicas compatíveis com a colite de derivação, e que estas mostraram-se reversíveis após a reconstrução do trânsito intestinal